Liver microfluidic control chip capable of realizing two-dimensional and three-dimensional cross co-culture and application thereof

Abstract

The invention relates to the technical field of microfluidic control and provides a liver microfluidic control chip capable of realizing two-dimensional and three-dimensional cross co-culture and application thereof. The microfluidic control chip comprises an upper-layer cover plate, an upper-layer substrate, an upper-layer porous membrane, an intermediate-layer substrate, a lower-layer porous membrane, a lower-layer substrate and a lower-layer cover plate; an upper-layer substrate culture chamber is formed in the upper-layer substrate; a lower-layer substrate culture chamber is formed in thelower-layer substrate; an intermediate-layer substrate culture chamber is arranged for the upper-layer porous membrane, the intermediate-layer substrate and the lower-layer porous membrane. The livermicrofluidic control chip capable of realizing the two-dimensional and three-dimensional cross co-culture and the application thereof provided by the invention have the benefits that the two-dimensional and three-dimensional cross co-culture of various cells can be realized on the chip, and further the in-vitro culture of a liver and other organs can be simulated; the size of each of the culture chambers on the chip is variable, so that different numbers of cell samples can be obtained, and further the flexible molecular biology test can be performed, such as RT-PCR and Western-blot; furthermore, the liver chip can be used to screen the hepatotoxicity of drugs and evaluate the activity of liver-protecting drugs.

Description

technical field [0001] The invention relates to a liver microfluidic chip for realizing two-dimensional and three-dimensional cross-culture and its application, belonging to the field of microfluidic technology. Background technique [0002] Microfluidics, also known as Lab-on-a-chip, is a science and technology that manipulates fluids in micron-scale space, which can prepare samples, The basic operation units such as reaction, separation, and detection are integrated on a micron-scale chip to automatically complete the entire analysis process. It is one of the most important cutting-edge technologies in the 21st century. It is considered to solve key problems such as high R&D costs and long cycles of innovative drugs, cosmetics and health products, and is a key technology to innovate the original technology system. It is facing a major development opportunity. and challenge. [0003] Organ on a chip is a subtype of microfluidic chip, which has been recognized by the indus...

AI Technical Summary

Problems solved by technology

However, the existing microfluidic liver chip model lacks such a highly biomimetic structure

For example, Alexander S. Mosig, et al constructed a perfusion cultured 3D liver model (Amicrofluidically perfused three dimensional human livermodel. BIOMATERIALS2015) using a microfluidic chip. HUVECs) and peripheral blood mononuclear macrophages ((PBMCs), the lower layer was inoculated with hepatic parenchymal cells (HepRG) and hepatic stellate cells (LX-2), and the upper layer was perfused with culture medium to simulate the liver microenvironment—the disadvantages of this structure It ignores the three-dimensional environment in which hepatic parenchymal cells grow, and cannot simulate the sinusoidal structure in the microenvironment

Mian Long, et al proposed a 3D assembled liver sinusoidal chip (Mimicking liver sinusoidal structures and functions using a3d-configured microfluidic chip.LAB CHIP 2017), which inoculated four kinds of isolated mouse liver cells in The two chambers of the chip, the upper layer is inoculated with liver blood sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), the lower layer is inoculated with hepatic parenchymal cells (HCs) and hepatic stellate cells (HSCs), the structure is largely simulated However, the two-dimensional growth of hepatic parenchymal cells and the 100uM distance between hepatic parenchymal cells and hepatic stellate cells greatly weakened the interconnection between the two

At the same time, the structure lacks a circulation pathway for bile

Images